SCN1A Mutation Analysis in Myoclonic Astatic Epilepsy and Severe Idiopathic Generalized Epilepsy of Infancy with Generalized Tonic-Clonic Seizures

Ebach, K.; Joos, Howard A.; Doose, H; Stephani, Ulrich; Kurlemann, G.; Fiedler, Barbara; Hahn, Andreas; Hauser, E. R.; Hundt, K.; Holthausen, Hans; Müller, Ulrich; Neubauer, Bernd A.

doi:10.1055/s-2005-865607

Cited by 53 publications

(21 citation statements)

References 10 publications

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“…A new point mutation in exon 20 of SCN1A has just been discovered in a family in which one brother has severe myoclonic epilepsy and one has Doose syndrome, probably inherited from a father who had one febrile seizure and a few generalized tonic–clonic seizures throughout his life 13 . However these genes have not been found consistently in sporadic cases, suggesting that these gene mutations are unlikely to be the primary cause of Doose syndrome 14,15 …”

Section: Geneticsmentioning

confidence: 99%

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Doose syndrome (myoclonic–astatic epilepsy): 40 years of progress

Kelley

Kossoff

2010

Develop Med Child Neuro

137

100

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Doose syndrome, otherwise traditionally known as myoclonic–astatic epilepsy, was first described as a unique epilepsy syndrome by Dr Hermann Doose in 1970. In 1989, the International League Against Epilepsy classified it formally as a symptomatic generalized epilepsy, and 20 years later it was renamed ‘epilepsy with myoclonic–atonic seizures’. In this review, we discuss the components of this unique disorder including its incidence, clinical features, and electroencephalographic findings. Recent evidence has suggested possible genetic links to the GEFS+ (generalized epilepsy with febrile seizures plus) family, and, additionally, some children with structural brain lesions can mimic the Doose syndrome phenotype. Treatment strategies such as corticosteroids, ethosuximide, and valproate have been described as only partially effective, but newer anticonvulsants, such as levetiracetam and zonisamide, may provide additional seizure control. The most effective treatment reported to date appears to be the ketogenic diet. Prognosis is quite varied in this disorder; however, many children can have a remarkably normal neurodevelopmental outcome.

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Section: Geneticsmentioning

confidence: 99%

“…13 However these genes have not been found consistently in sporadic cases, suggesting that these gene mutations are unlikely to be the primary cause of Doose syndrome. 14,15 TREATMENT Doose syndrome is historically described as difficult to treat.…”

Section: Geneticsmentioning

confidence: 99%

Doose syndrome (myoclonic–astatic epilepsy): 40 years of progress

Kelley

Kossoff

2010

Develop Med Child Neuro

137

100

View full text Add to dashboard Cite

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“…Mutation analysis of SCN1A using PCR-based sequencing has identified point mutations, small deletions, and insertions that were mostly de novo in about 30 to 70% of SMEI patients [Claes et al, 2001[Claes et al, , 2003Sugawara et al, 2002;Ohmori et al, 2002;Fujiwara et al, 2003;Gennaro et al, 2003;Nabbout et al, 2003;Wallace et al, 2003;Fukuma et al, 2004;Ceulemans et al, 2004;Ebach et al, 2005;Kimura et al, 2005]. This implies that in the remaining 30 to 70% of SMEI patients without a ''classical'' SCN1A mutation, other types of mutations in SCN1A such as microdeletions comprising the gene, mutations in regulatory sequences, or mutations in other genes might be the underlying cause.…”

Section: Introductionmentioning

confidence: 98%

Microdeletions involving theSCN1A gene may be common inSCN1A-mutation-negative SMEI patients

et al. 2006

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Severe myoclonic epilepsy of infancy (SMEI) or Dravet syndrome is a rare epilepsy syndrome. In 30 to 70% of SMEI patients, truncating and missense mutations in the neuronal voltage-gated sodium-channel alpha-subunit gene (SCN1A) have been identified. The majority of patients have truncating mutations that are predicted to be loss-of-function alleles. Because mutation detection studies use PCR-based sequencing or conformation sensitive gel electrophoresis (CSGE), microdeletions, which are also predicted to be loss-of-function alleles, can easily escape detection. We selected 11 SMEI patients with or without additional features who had no SCN1A mutation detectable with sequencing analysis. In addition, none of the patients was heterozygous for any of the SNPs in SCN1A, indicating that they were either homozygous for all SNPs or hemizygous due to a microdeletion of the gene. We subsequently analyzed these patients for the presence of microdeletions in SCN1A using a quantitative PCR method named multiplex amplicon quantification (MAQ), and observed three patients missing one copy of the SCN1A gene. All three microdeletions were confirmed by fluorescence in situ hybridization (FISH). These findings demonstrate that a substantial percentage of SCN1A-mutation-negative SMEI patients with or without additional features carry a chromosomal microdeletion comprising the SCN1A gene and that haploinsufficiency of the SCN1A gene is a cause of SMEI.

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“…However, in some patients not all phenotypic features are present which has been described as SMEI borderline (BSME or SMEB) (Ohmori et al, 2003;. Also, other phenotypes like intractable childhood epilespsy with generalized tonic clonic seizures (ICEGTC) , severe idiopathic epilepsy of infancy (SIGEI) (Ebach et al, 2005) and severe infantile multifocal epilepsy (SIMFE) resemble SMEI. These phenotypes are all part of the GEFS+ spectrum which starts with benign FS and ends with SMEI as its most severe form .…”

Section: Description Of Phenotypesmentioning

confidence: 99%

TheSCN1Avariant database: a novel research and diagnostic tool

et al. 2009

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ABSTRACT:The neuronal voltage-gated sodium channel Na v 1.1 encoded by the SCN1A gene plays an important role in the generation and propagation of action potentials in the central nervous system. Altered function of this channel due to mutations in SCN1A leads to hypersynchronous neuronal discharges resulting in seizures or migrainous attaques. A large number of distinct sequence variants in SCN1A are associated with diverse epilepsy and migraine syndromes. We developed an online and freely available database containing all reported sequence variants in SCN1A (http://www.molgen.ua.ac.be/SCN1AMutations/). We verified 623 distinct sequence variants, listed them using standard nomenclature for description and classified them according to their putative pathogenic nature. We provided links to relevant publications and information on the associated phenotype. The database can be queried using cDNA or protein position, phenotype, variant type or publication. By listing all SCN1A variants in a comprehensive manner, this database will facilitate interpretation of newly identified sequence variants and provide better insight into the genotype-phenotype relations of the growing number of SCN1A mutations.

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SCN1A Mutation Analysis in Myoclonic Astatic Epilepsy and Severe Idiopathic Generalized Epilepsy of Infancy with Generalized Tonic-Clonic Seizures

Cited by 53 publications

References 10 publications

Doose syndrome (myoclonic–astatic epilepsy): 40 years of progress

Doose syndrome (myoclonic–astatic epilepsy): 40 years of progress

Microdeletions involving theSCN1A gene may be common inSCN1A-mutation-negative SMEI patients

TheSCN1Avariant database: a novel research and diagnostic tool

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